Protein Engineering And In Vitro Characterization Of A Factor Viia Analog With Selective Abrogation Of Tissue Factor Binding

Background Recombinant FVIIa (NovoSeven®) is used for the treatment of spontaneous bleeds in haemophilia patients with inhibitory antibodies against FVIII or FIX. Two theories have been proposed to describe the mechanism of action of FVIIa (van’t Veer C et. al., (2000) Blood 95:1330-5, Monroe DM et. al., (1998) Blood Coagulation Fibrinolysis 9(S1):S15-S20); a) competition with zymogen FVII to bind to surface exposed TF at site of injury, and b) activation of FX by FVIIa bound to phospholipids exposed on activated platelets. This study aims at generation and characterization of a novel reagent that will provide new insights into the extent of TF influence in vascular injury.